Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.
Office of Population Research, Princeton University, Princeton, NJ 08544, USA.
Nat Ecol Evol. 2017 Nov;1(11):1766-1772. doi: 10.1038/s41559-017-0315-3. Epub 2017 Sep 25.
A fundamental challenge faced by the immune system is to discriminate contexts meriting activation from contexts in which activation would be harmful. Selection pressures on this ability are likely to be acute: the penalty of mis-identification of pathogens (therefore failure to attack them) is mortality or morbidity linked to infectious disease, which could reduce fitness by reducing lifespan or fertility; the penalty associated with mis-identification of host (therefore self-attack) is immunopathology, whose fitness costs can also be extreme. Here we use classic epidemiological tools to frame this trade-off between sensitivity and specificity of immune activation, exploring implications for evolution of immune discrimination. We capture the expected increase in the evolutionarily optimal sensitivity under higher pathogen mortality risk, and a decrease in sensitivity with increased immunopathology mortality risk; but a number of non-intuitive predictions also emerge. All else being equal, optimal sensitivity decreases with increasing lifespan; and, where sensitivity can vary over age, decreases at late ages not solely attributable to immunosenescence are predicted. These results both enrich and challenge previous predictions concerning the relationship between life expectancy and optimal evolved defenses, highlighting the need to account for epidemiological setting, lifestage-specific immune priorities, and immune discrimination in future investigations.
免疫系统面临的一个基本挑战是区分需要激活的情况与激活可能有害的情况。这种能力的选择压力可能很严峻：错误识别病原体（因此未能攻击它们）的代价是与传染病相关的死亡率或发病率，这可能会通过降低寿命或生育能力来降低适应性；错误识别宿主（因此自我攻击）的代价是免疫病理学，其适应性成本也可能非常高。在这里，我们使用经典的流行病学工具来构建免疫激活的敏感性和特异性之间的这种权衡，并探讨其对免疫识别进化的影响。我们捕捉到了在更高的病原体死亡率风险下，进化上最佳敏感性预期增加，以及随着免疫病理学死亡率风险增加而敏感性降低的情况；但也出现了一些非直观的预测。在其他条件相同的情况下，最佳敏感性随寿命的增加而降低；而且，如果敏感性可以随年龄变化，那么预测到的敏感性在老年时下降并不完全归因于免疫衰老。这些结果丰富并挑战了以前关于预期寿命和最佳进化防御之间关系的预测，突出了在未来的研究中需要考虑流行病学背景、特定生命阶段的免疫优先级和免疫识别。
